137 research outputs found

    Pharmacy Placements in General Practice

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    Description: The role of pharmacists in General Practice has received increasing attention, with the RPS, RCGP and the NHS Alliance all coming out in support and promoting the role that pharmacists can play. However, in order for pharmacists to fulfil this role, it is important that they understand the general practice environment and the needs and opportunities for pharmacists. It is equally important that pharmacists practising in community pharmacy and hospital pharmacy also understand the general practice setting in order that they can optimise how they work with GPs to support transfer of care and enable patients to understand and effectively manage their long term conditions and medication. By understanding the processes and priorities of general practice, pharmacy students entering any sector of practice should be able to better work with general practice as part of a multidisciplinary and cross-care boundary team. At the University of Sunderland, an Academic Practitioner post was created in collaboration with Sunderland CCG, enabling an opportunity for undergraduate professional placements to be delivered in general practice. It was decided that the placement would fit best at Stage 3 of the MPharm programme at the University of Sunderland, linking with clinical topics such as diabetes which are introduced at this stage, and using a clinical topic which had been covered previously, COPD (covered in Stage 2) to introduce the new concept of the Quality and Outcomes Framework and to also contribute to spiral learning. There had been previously been success in using a rotational ‘station’ based model of placement delivery as part of the MPharm programme with other providers and a similar model was adopted for the general practice placements. Students rotated around four ‘stations’ which included: • Exploring the role of a general practice administrator • Observing a practice nurse clinic for chronic conditions • A diabetes case study utilising a general practice clinical system • An introduction to the Quality and Outcomes Framework (QOF) Process or Method of Implementation: Requests for general practices to deliver placements were presented at local training events and via email using SCCG networks. A briefing sheet which included the requirements of the practice to deliver the placements was created and distributed to ensure that practices could deliver the placements as designed. The format and materials for placement delivery were designed by the link post, general practices and a primary care medicines optimisation service provider which was procured to support placement delivery. GP practice support pharmacists facilitated the placements. Challenges faced and learning points: Learning points • Protocols can be used to build patient profiles in EMIS Web for case studies • Utilising a medicines optimisation provider enabled smoother and more authentic delivery of placements • Students valued the opportunity to see patients in practice nurse clinics • The opportunity to use a GP clinical system was noted by students as being a useful exercise • Spending time with general practice administration staff provided insight into repeat prescription processes and appointments which they could reconcile with their community pharmacy placement experiences Challenges • Practice nurse clinics did sometimes not often run for long enough to accommodate all rotations of the placement • Accommodating 2 students within a consultation room for observation was sometimes difficult due to space restrictions in rooms • Students were often more proficient than anticipated at working through case studies, so these will be expanded for the next iteration of placements Summary of perceived benefits to patients, pharmacy and the NHS: Pharmacy undergraduates have had an introduction to the general practice environment which will support future multidisciplinary and cross-boundary working regardless of future setting. The placement may increase the number of pharmacists entering general practice based roles following registration

    Fluorescence Guided Surgery: Intra-Operative Fluorescent Imaging in Laparoscopic Colonic Tumour Resection and Laparoscopic Cholecystectomy Surgery

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    Introduction: Fluorescence-guided surgery could improve the operative decision-making process. Near Infrared Cholangiography (NIR-FC) with Indocyanine Green (ICG) in laparoscopic cholecystectomy (LC) may aid visualisation of bile duct anatomy. The c-met transmembrane protein is over-expressed in colorectal cancer (CRC). EMI-137 is a c-Met specific peptide coupled to fluorophore. Methods: Twenty-two participants requiring LC were allocated to four dosing subgroups and received a single intravenous (I.V) dose of ICG before surgery. Biliary anatomy was assessed with NIR-FC and surgeon satisfaction was evaluated. c-Met transcription in HT-29 CRC cells was silenced with targeted SiRNA to demonstrate specificity of EMI-137. A HT-29 xenograft model was developed in female BALB/C mice. EMI-137 (0.18mg/kg) was injected into tail veins and biodistribution analysed by fluorescent imaging. c-Met immunopositivity was graded in matched normal and CRC tissue TMA samples obtained from the MRC CLASICC trial. Nine participants with colon cancer, received IV EMI-137 1-3 hours before laparoscopic tumour resection surgery. Tumour and lymph node (LN) fluorescence were assessed with a fluorescent laparoscope. Immunohistochemistry analysed c-Met expression. Results: A prolonged ICG dosing interval consistently increased structure identification at LC and was preferred by the operating surgeon. c-Met was consistently overexpressed in CRC relative to normal tissue and could be visualised with EMI-137, comparable to indirect c-Met identification methods. EMI-137 uptake in tumour xenografts was observed for 6 hours post-administration. At clinical trial, no serious adverse events related to EMI-137 were reported. Marked background fluorescence was observed in all participants; 4/9 showed mild increase in tumour fluorescence over background; 5/9 had histological LN metastases; no fluorescent LN were detected intraoperatively. All primary tumours (8/8) and malignant LN (15) exhibited moderate-high c-Met protein expression. Conclusion: Prolonged ICG dosing improves visualisation of structures with NIR-FC at LC. EMI-137, binds specifically to the human c-Met protein, is safe but its intra-operative utility is limited by insufficient tumour-to-background ratios

    Opportunities for mesoporous nanocrystalline SnO2 electrodes in kinetic and catalytic analyses of redox proteins

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    PFV (protein film voltammetry) allows kinetic analysis of redox and coupled-chemical events. However, the voltammograms report on the electron transfer through a flow of electrical current such that simultaneous spectroscopy is required for chemical insights into the species involved. Mesoporous nanocrystalline SnO2 electrodes provide opportunities for such ‘spectroelectrochemical’ analyses through their high surface area and optical transparency at visible wavelengths. Here, we illustrate kinetic and mechanistic insights that may be afforded by working with such electrodes through studies of Escherichia coli NrfA, a pentahaem cytochrome with nitrite and nitric oxide reductase activities. In addition, we demonstrate that the ability to characterize electrocatalytically active protein films by MCD (magnetic circular dichroism) spectroscopy is an advance that should ultimately assist our efforts to resolve catalytic intermediates in many redox enzymes

    An Investigation into the Protein Composition of the Teneral Glossina morsitans morsitans Peritrophic Matrix.

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    BACKGROUND Tsetse flies serve as biological vectors for several species of African trypanosomes. In order to survive, proliferate and establish a midgut infection, trypanosomes must cross the tsetse fly peritrophic matrix (PM), which is an acellular gut lining surrounding the blood meal. Crossing of this multi-layered structure occurs at least twice during parasite migration and development, but the mechanism of how trypanosomes do so is not understood. In order to better comprehend the molecular events surrounding trypanosome penetration of the tsetse PM, a mass spectrometry-based approach was applied to investigate the PM protein composition using Glossina morsitans morsitans as a model organism. METHODS PMs from male teneral (young, unfed) flies were dissected, solubilised in urea/SDS buffer and the proteins precipitated with cold acetone/TCA. The PM proteins were either subjected to an in-solution tryptic digestion or fractionated on 1D SDS-PAGE, and the resulting bands digested using trypsin. The tryptic fragments from both preparations were purified and analysed by LC-MS/MS. RESULTS Overall, nearly 300 proteins were identified from both analyses, several of those containing signature Chitin Binding Domains (CBD), including novel peritrophins and peritrophin-like glycoproteins, which are essential in maintaining PM architecture and may act as trypanosome adhesins. Furthermore, 27 proteins from the tsetse secondary endosymbiont, Sodalis glossinidius, were also identified, suggesting this bacterium is probably in close association with the tsetse PM. CONCLUSION To our knowledge this is the first report on the protein composition of teneral G. m. morsitans, an important vector of African trypanosomes. Further functional analyses of these proteins will lead to a better understanding of the tsetse physiology and may help identify potential molecular targets to block trypanosome development within the tsetse

    The relationship between redox enzyme activity and electrochemical potential—cellular and mechanistic implications from protein film electrochemistry

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    In protein film electrochemistry a redox protein of interest is studied as an electroactive film adsorbed on an electrode surface. For redox enzymes this configuration allows quantification of the relationship between catalytic activity and electrochemical potential. Considered as a function of enzyme environment, i.e., pH, substrate concentration etc., the activity–potential relationship provides a fingerprint of activity unique to a given enzyme. Here we consider the nature of the activity–potential relationship in terms of both its cellular impact and its origin in the structure and catalytic mechanism of the enzyme. We propose that the activity–potential relationship of a redox enzyme is tuned to facilitate cellular function and highlight opportunities to test this hypothesis through computational, structural, biochemical and cellular studies

    Synthesis of an alkylmagnesium amide and interception of a ring-opened isomer of the important utility amide 2,2,6,6-tetramethylpiperidide (TMP)

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    Two new magnesium complexes containing the important utility amide 2,2,6,6-tetramethylpiperidide (TMP) have been synthesised. Treating the magnesium bis(alkyl) reagent (Me3SiCH2)2Mg with a molar equivalent of TMP(H) in hydrocarbon medium produces the dimeric alkylmagnesium amide complex [(Me3SiCH2)Mg(μ-TMP)]22, which was isolated in high yield. X-ray crystallography revealed that 2 was an unsymmetrical dimer as unusually the two TMP ligands adopt different conformations – one a chair, the other a twisted boat. Solution studies (multinuclear NMR and DOSY NMR spectroscopies) show that 2 undergoes a monomerisation and Schlenk equilibrium in d8-THF. When (Me3SiCH2)2Mg was reacted with two molar equivalents of TMP(H) in hydrocarbon medium [in an effort to prepare Mg(TMP)2] a crystalline sample of a surprising product, a tetranuclear triheteroanionic amide-alkoxide-amidoalkene [(TMP)Mg(μ-TMP){μ-N(H)C(Me)2CH2CH2CH2C(Me) = CH2}Mg(μ-OCH2SiMe3)]23 was obtained. Complex 3 contains two unexpected anions, namely the alkoxide produced via oxygen insertion into a Mg–C bond, and the primary amidoalkene which is produced via ring opening of the TMP anion

    The preparation of large surface area lanthanum based perovskite supports for AuPt nanoparticles: tuning the glycerol oxidation reaction pathway by switching the perovskite B site

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    Gold and gold alloys, in the form of supported nanoparticles, have been shown over the last three decades to be highly effective oxidation catalysts. Mixed metal oxide perovskites, with their high structural tolerance, are ideal for investigating how changes in the chemical composition of supports affect the catalysts' properties, while retaining similar surface areas, morphologies and metal co-ordinations. However, a significant disadvantage of using perovskites as supports is their high crystallinity and small surface area. We report the use of a supercritical carbon dioxide anti-solvent precipitation methodology to prepare large surface area lanthanum based perovskites, making the deposition of 1 wt% AuPt nanoparticles feasible. These catalysts were used for the selective oxidation of glycerol. By changing the elemental composition of the perovskite B site, we dramatically altered the reaction pathway between a sequential oxidation route to glyceric or tartronic acid and a dehydration reaction pathway to lactic acid. Selectivity profiles were correlated to reported oxygen adsorption capacities of the perovskite supports and also to changes in the AuPt nanoparticle morphologies. Extended time on line analysis using the best oxidation catalyst (AuPt/LaMnO3) produced an exceptionally high tartronic acid yield. LaMnO3 produced from alternative preparation methods was found to have lower activities, but gave comparable selectivity profiles to that produced using the supercritical carbon dioxide anti-solvent precipitation methodology
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